Organization of Host Afferents to Cerebellar Grafts Implanted into Kainate Lesioned Cerebellum in Adult Rats

This paper examines the organization of host afferents within cerebellar grafts implanted into kainic acid lesioned cerebellum. Our selection of a cerebellum, a prime example of a 'point-to-point' system, permits precise determination of the degree and the specificity of host-graft interactions. One month after a cerebellar injection of kainic acid, the lesion produced can be divided into two concentric regions: (i) a central necrotic zone, totally depleted of neurons (zone 1), and (ii) a peripheral zone which lacks all Purkinje cells but preserves its cortical lamination (zone 2). Two months after the implantation of solid pieces of embryonic cerebellum, the graft has evolved into a minicerebellar structure, occupying most of zone 1. The grafted minicerebellum consists of a highly convoluted trilaminated cortex with a core containing deep nuclear neurons. Purkinje cells are positioned between the molecular and granular layer with their short and irregular dendrites branching within the former. Donor foetal Purkinje cells migrate into the contiguous portion of the molecular layer of the host zone 2. These embryonic neurons set up within the upper three-quarters of the host molecular layer, and develop monoplanar dendritic trees that span the whole width of the layer. The organization of host-graft interactions was studied by autoradiography of anterogradely transported tritiated leucine, injected in the host bulbar region containing the caudal half of the inferior olivary complex (origin of all vermal climbing fibres) and the dorsally adjacent paramedian reticular nucleus (origin of a few mossy fibres). Numerous labelled fibres cross the host-graft interface from the white matter of the host cerebellum, and provide innervation to the minicerebellar structure. The vast majority of these labelled axons terminate in the molecular layer, forming axonal arborizations that follow the shape of the Purkinje cell dendrites. The labelled climbing fibres are organized into uneven sagittally aligned strips, which mimic that of olivocerebellar projections in control rats. Only a small proportion of host labelled fibres end in the donor granular layer, forming typical mossy fibre rosettes. The latter are present in the region of the graft close to the host-graft interface. In addition, labelled axons are observed climbing over the dendritic trees of grafted Purkinje cells that have invaded a portion of the host molecular layer of zone 2. In all regions containing grafted Purkinje cells and labelled climbing fibres, the density of the innervation is close to normal with practically all Purkinje cells receiving a climbing fibre. The extensive integration of the grafted cells into the deficient neuronal networks of the host clearly illustrates the positive neurotropic effect exerted by immature cerebellar neurons on adult extracerebellar afferent fibres. The hodological integration, allowing a possible restoration of the impaired cerebellar circuitry, takes place respecting the specificity and topographic distribution which characterize the 'point-to-point' arrangement of normal cerebellar circuitry.